The impact of 2023 EMA recommendations on patients treated with JAK inhibitors: real-life experience from a prospective monocentric cohort

EAR E DITOR , The Janus kinase inhibitors (JAKis) are a promising class of drugs for treating immune-mediated diseases

DEAR EDITOR, The Janus kinase inhibitors (JAKis) are a promising class of drugs for treating immune-mediated diseases [1].However, recent data suggest that JAKis may be associated with an increased risk of cardiovascular and thromboembolic events and malignancies [2,3].As a result, the European Medicines Agency (EMA) recommends that these drugs should be used in patients !65 years of age or those at increased risk of major cardiovascular events (MACE) and cancer only if no suitable alternatives are available [4].Moreover, the EMA also suggests caution when using JAKis in patients with risk factors for venous thromboembolism (VTE) [5].The EULAR advocates for shared decision making between the patient and rheumatologist when treating patients with arthritis [6].
This study prospectively evaluated the impact of the EMA recommendations on the management of patients with rheumatic diseases already on JAKi treatment at a tertiary Italian hospital.We enrolled all consecutive patients on JAKi with a scheduled follow-up visit between December 2022 and April 2023 and collected data on the patients' age, previous therapies and history of/risk factors for MACE, VTE and cancer.All patients, regardless of age and comorbidities, discussed with the rheumatologist the new EMA recommendations and the opportunity of maintaining or discontinuing JAKi based on such recommendations.The final decision, the reason(s) for that decision and whether the decision was primarily led by the physician or patient were recorded.All patients provided consent for anonymous use of their demographic and clinical data.
We evaluated 223 patients with rheumatic diseases on JAKi (Supplementary Table S1, available at Rheumatology online, summarizes their main demographic and clinical characteristics).Following the visit, JAKi treatment was interrupted in 29 (13%) patients.In all cases, the patient and rheumatologist shared the decision, as advocated by the EULAR recommendations [6].In 3 patients (10%), the decision was primarily led by the patient due to concerns regarding the risk of MACE or cancer.In 26 patients (90%), the rheumatologist was the first to propose a therapeutic modification.The medical history of patients who withdrew JAKi and reasons that led to the decision to withdraw JAKi are described in detail in Table 1.The mean age of patients who changed therapy was 66 years (S.D. 11) and 17 of them (59%) were !65 years of age.Nineteen patients (73%) had at least one cardiovascular risk factor.The most common cardiovascular risk factor among patients who changed treatment was dyslipidaemia [n ¼ 16 (55%)], followed by smoking [n ¼ 13 (45%)], hypertension [n ¼ 12 (41%)], diabetes [n ¼ 8 (28%)], obesity [n ¼ 2 (7%)] and chronic coronary disease [n ¼ 2 (7%)].A previous diagnosis of cancer and deep vein thrombosis was present in 4 (14%) and 2 (7%) patients, respectively.No patient had a previous history of acute coronary syndrome or stroke/transient ischaemic attack.Among patients who suspended JAKi, in 12 cases (41%) this decision was primarily made because the drug was deemed primarily (75%) or secondarily (25%) ineffective by the rheumatologist (i.e.patients had moderate or high disease activity at clinical evaluation).Hence, among patients who were adequately responding to JAKi, only 17/ 211 (8%) changed the treatment.After JAKi withdrawal, patients were swapped to TNF inhibitors Six patients (21%) were maintained on conventional synthetic DMARD monotherapy.
In conclusion, our data show that only a very small proportion of patients with arthritis treated with JAKi requested therapy discontinuation due to concerns about the recent EMA recommendations [3].This testifies to a general confidence of patients to continue receiving JAKi if they are Accepted: 22 July 2023 V C The Author(s) 2023.Published by Oxford University Press on behalf of the British Society for Rheumatology.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/),which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.provided with adequate information.In most cases, the rheumatologists themselves proposed the treatment modification due to various factors, mostly the patients' age and the presence of cardiovascular risk factors.Moreover, in nearly half of patients who suspended JAKi, a lack of efficacy (mostly secondary inefficacy) was the reason that led to the final decision.On the other hand, it is worth noting that, in our cohort, JAKi therapy ensured optimal disease control overall, as evidenced by the relatively low fraction of patients with moderate/high disease activity (5%).
The strengths of this study are its prospective nature, the large number of patients included from a monocentric cohort and their demographic heterogeneity.The main shortcoming is the absence of data on the outcome of patients who withdrew JAKi.A comparison of our findings with those from other cohorts to further confirm these data is certainly warranted.

Table 1 .
Demographic features and clinical history of patients with rheumatic diseases who stopped a JAKi between December 2022 and April 2023